Growth Hormone Treatment of Children with Idiopathic Short Stature or Growth Hormone Sufficient Growth Failure

The efficacy of growth hormone (GH) treatment in children with idiopathic growth failure has been the subject of controversy because of ethical concerns (1,2), financial considerations (3) and variable adult height outcomes (4,5). Much of the disagreement about the benefits of GH treatment relates to the heterogeneity of the study populations receiving therapy. Ideally, the efficacy of GH therapy should be based on the height outcomes of homogeneous populations of pathologically short children rather than the adult heights of children with variable shortness of differing etiologies. Published studies have sometimes combined children who had constitutional delay of growth and adolescence with subjects who had either severe genetic short stature or significant growth failure growth failure based on abnormal heights and growth rates for chronological age. These short children have been classified by various terminologies: Normal Variant Short Stature (NVSS), Idiopathic Short Stature (ISS), Constitutional Delay of Growth and Puberty (CGDP), GH neurosecretory dysfunction, idiopathic growth failure, and non-GH deficient short stature. Without treatment, the height outcomes in most studies have failed to reach mid-parental target height. In contrast, GH therapy has resulted in mixed height outcomes; some patients reached or exceeded genetic target height whereas others did not. Given the high cost and potential risk of adverse events, some authors have criticized the use of GH in healthy very short children without a documented endocrine disorder (1). Some of this disagreement may be resolved as we improve our ability to identify mutations in various growth regulating genes such as SHOX, GHRH, Ghrelin, GHRP, Pit-1, Prop-1, GH and their receptors.